These studies are designed to determine the role of alpha-CaMKII in memory formation. Specifically, the effects of alpha-CaMKII deletion in distinct hippocampus subregions (CA1, dentate gyrus) will be examined. Deletion of alpha-CAMKII will be accomplished using contemporary knockout technology and targeted viral-vector infusions. Electrophysiological analyses will determine the effects of alpha-CaMKII deletion on long-term potentiation (LTP), a cellular model of learning and memory. Behavioral analyses will examine the effects of alpha-CaMKII loss on specific mnemonic functions mediated by each hippocampus subregion. The ultimate goal of these studies is to further our understanding of the molecular mechanisms that underlie memory formation in humans. Hippocampal dysfunction caused by disease (e.g., Alzheimer's, Korsakoff's), aging or damage produces severe memory loss. Understanding the molecular mechanisms that underlie hippocampus-dependent memory formation should provide insight into disorders caused by the dysfunction of this brain region.